EUS-guided versus direct endoscopic cyanoacrylate injection for variceal eradication: A systematic review and meta-analysis of randomized controlled trials

While direct endoscopic cyanoacrylate injection (DEI-CYA) is the standard hemostatic therapy, it is associated with risks of ectopic embolization and ulceration. EUS–guided injection (EUS-CYA) allows for precise targeting of feeder vessels, potentially improving outcomes. A comprehensive search was conducted across PubMed, Web of Science, CENTRAL, and Scopus for RCTs up to January 2026. Primary outcomes included early and late rebleeding rates and variceal eradication. Risk ratios (RRs) and standardized mean differences (SMD) were pooled using a random-effects model. Five RCTs involving 440 patients were included. EUS-CYA was associated with a significant reduction in late rebleeding compared with DEI-CYA (RR: 0.40; 95% confidence intervals [CI]: 0.27–0.60; P < 0.001). However, there was no significant difference in early rebleeding ( P = 0.53) or overall variceal eradication rates (RR: 1.13; 95% CI: 0.97–1.31; P = 0.11). Regarding safety, EUS-CYA significantly reduced the risk of postinjection ulcers (RR: 0.32; 95% CI: 0.11–0.93; P = 0.04), while rates of ectopic embolism ( P = 0.75) and mortality ( P = 0.65) were comparable. Procedurally, EUS-CYA was more efficient, requiring significantly less cyanoacrylate (SMD: −0.35; 95% CI: −0.61 to −0.09; P = 0.01) and fewer sessions for eradication (SMD: −1.28; 95% CI: −2.50 to −0.05; P = 0.04). Current evidence suggests that EUS-CYA likely reduces the risk of late rebleeding compared with DEI-CYA. While the data indicate potential benefits regarding procedural efficiency (reduced cyanoacrylate volume and fewer sessions) and a lower incidence of postinjection ulcers, the certainty of evidence for these outcomes remains very low.